Table 4.
Targeted drugs and clinical trials related to the proteasome
| Drug | Disease | Trial name | Phase | Status | ORR/CR | NCT# | Reference |
|---|---|---|---|---|---|---|---|
| Proteasome inhibitor | |||||||
| Bortezomib | A reversible proteasome inhibitor binding primarily with β5 and to a lesser extent, with β2 and β1 of the 20S proteasome particle | ||||||
| Bortezomib | Relapsed or refractory MCL | Bortezomib in subjects with relapsed or refractory mantle cell lymphoma | 2 | Completed | 31%/8% | NCT00063713 | 281 |
| Bortezomib, panobinostat | Relapsed or refractory PTCL | Study of bortezomib and panobinostat in treating patients with relapsed or refractory peripheral T-cell lymphoma | 2 | Completed | 43%/22% | NCT00901147 | 282 |
| Bortezomib, ibrutinib | MCL | Combination of ibrutinib and bortezomib to treat patients with mantle cell lymphoma | 1/2 | Recruiting | – | NCT02356458 | – |
| Bortezomib, dexamethasone | Relapsed or refractory CTCL | Bortezomib plus dexamethasone therapy in patients with relapsed or refractory cutaneous T-cell lymphoma | 2 | Recruiting | – | NCT03487133 | – |
| Bortezomib, GDP | Non-GCB DLBCL | A study of bortezomib plus GDP in the treatment of relapsed or refractory non-GCB DLBCL | 2 | Unknown | – | NCT02542111 | – |
| Bortezomib, CHOP | Advanced aggressive T-NHLs/NKTCL | Bortezomib and CHOP in patients with advanced-stage aggressive T-cell or NK/T-cell lymphoma | 1/2 | Completed | NA | NCT00374699 | – |
| VR-CAP vs. R-CHOP | Untreated MCL | Study of the combination of rituximab, cyclophosphamide, doxorubicin, bortezomib, and prednisone or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with newly diagnosed mantle cell lymphoma | 3 | Completed | NA | NCT00722137 | 283 |
| Bortezomib, dexamethasone, rituximab | Untreated WM | Bortezomib, low-dose dexamethasone, and rituximab in untreated Waldenström’s macroglobulinemia | 2 | Completed | 85%/3% | NCT00981708 | 284 |
| Bortezomib, dexamethasone, rituximab, and cyclophosphamide | WM | Efficacy of First-Line Dexamethasone, Rituximab, and Cyclophosphamide +/− Bortezomib for Patients With Waldenström’s Macroglobulinemia | 3 | Active, not recruiting | – | NCT01788020 | – |
| Carfilzomib | A second-generation irreversible proteasome inhibitor binding to the β5 subunit of the 20S proteasome particle | ||||||
| Carfilzomib | Relapsed or refractory T-NHLs | Carfilzomib in treating patients with relapsed or refractory T-cell lymphoma | 1 | Completed | NA | NCT01336920 | – |
| Carfilzomib, vorinostat | Relapsed or refractory lymphoma | Study of carfilzomib and vorinostat for relapsed or refractory lymphoma | 1 | Completed | NA | NCT01276717 | – |
| Carfilzomib, romidepsin | Relapsed or refractory PTCL | Evaluation of the combination of romidepsin and carfilzomib in relapsed or refractory peripheral T-cell lymphoma patients | 1/2 | Recruiting | – | NCT03141203 | – |
| Carfilzomib, umbralisib | Relapsed or refractory lymphoma | Carfilzomib and umbralisib in treatment of relapsed or refractory lymphoma | 1/2 | Recruiting | – | NCT02867618 | – |
| Carfilzomib, rituximab | WM/MZL | Carfilzomib with or without rituximab in the treatment of Waldenström’s macroglobulinemia or marginal zone lymphoma | 2 | Completed | NA | NCT03269552 | – |
| Carfilzomib, bendamustine, rituximab | Relapsed or refractory NHLs | Carfilzomib with bendamustine and rituximab in patients with relapsed or refractory non-Hodgkin’s lymphoma | 1 | Recruiting | – | NCT02187133 | – |
| Carfilzomib, R-CHOP | DLBCL | Carfilzomib, rituximab, and combination chemotherapy in treating patients with diffuse large B-cell lymphoma | 1/2 | Recruiting | – | NCT02073097 | – |
| Carfilzomib, R-ICE | Relapsed or refractory DLBCL | Carfilzomib, rituximab, ifosfamide, carboplatin, and etoposide in treating patients with relapsed or refractory stage I-IV diffuse large B-cell lymphoma | 1/2 | Recruiting | – | NCT01959698 | – |
| Ixazomib | A reversible proteasome inhibitor binding to the β5 subunit of the 20S proteasome particle | ||||||
| Ixazomib | Relapsed or refractory FL | Phase 2 study of oral ixazomib in adult patients with relapsed or refractory follicular lymphoma | 2 | Completed | PSMB1 positice, 8.3%/0%; PSMB1 negative, 0%/0% | NCT01939899 | – |
| Ixazomib | Relapsed or refractory CTCL/PTCL | Open-label, phase 2 study of ixazomib in patients with relapsed or refractory cutaneous and peripheral T-cell lymphoma | 2 | Completed | 67%/NA | NCT02158975 | – |
| Ixazomib, rituximab | Indolent B-NHLs | Ixazomib and rituximab in treating patients with indolent B-cell non-Hodgkin’s lymphoma | 2 | Recruiting | – | NCT02339922 | – |
| Ixazomib, ibrutinib | Relapsed or refractory MCL | A study of ixazomib and ibrutinib in relapsed or refractory mantle cell lymphoma | 1/2 | Recruiting | – | NCT03323151 | – |
| Ixazomib, romidepsin | Relapsed or refractory PTCL | Study of ixazomib and romidepsin in peripheral T-cell lymphoma | 1/2 | Recruiting | – | NCT03547700 | – |
| lenalidomide, ixazomib, rituximab | High-risk indolent B-NHLs | Lenalidomide, ixazomib, and rituximab as frontline therapy for high-risk indolent B-cell lymphoma | 1/2 | Active, not recruiting | – | NCT02898259 | – |
NA: ORR or CR are not available on the clinicaltrials.gov or from the published article, although the trial has been completed
GDP gemcitabine, dexamethasone, and cisplatin, CHOP cyclophosphamide, doxorubicin, vincristine, prednisolone, VR-CAP bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone, R-CHOP rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone, R-ICE rituximab, ifosfamide, carboplatin, etoposide, PSMB1 proteasome subunit beta type-1